DESCRIPTION (Applicant's abstract): The Inattentive subtype (IN) of Aftention-Deficit/Hyperactivity Disorder was newly defined in DSM-IV (1994). Recent epidemiological studies suggest that IN is at least as common and as impairing academically and socially as the more commonly recognized Combined type (CB). However, little is known about the etiology, course and outcome, or treatment of the IN type. Notably, although stimulant drugs are commonly used clinically to treat the disorder, there have been no systematic studies of its efficacy in the IN subtype. Differences between the IN and CB subtypes in behavioral phenotype, as well as in gender ratio, age of onset, and comorbidity suggest there may be critical differences in neurobiology, which may have relevance for response to drug treatments. The lack of data concerning stimulant drug efficacy in the IN type thus constitutes an important issue from the perspective of public health and quality of care. The proposed research is responsive to the current RFA in that it will study the efficacy of an established treatment (stimulants) in a new patient population (the IN subtype). The proposed project will assess and compare the response of the IN and CB subtypes to placebo and low, medium, and high doses of immediate-release methylphenidate in a double-blind crossover trial with one week of exposure to each condition. Order of conditions will be counterbalanced. Twenty-four male and female children between the ages of 7 and 12 will be enrolled in each group. Outcome measures will include weekly ratings by parents and teachers on wellnormed measures of ADHD symptoms and functional impairment previously shown to be drug-sensitive (Conners and SKAMP scales). In addition, children will be examined and rated weekly by a child psychiatrist on a measure of Clinical Global Improvement. A second specific aim is to test a hypothesis, emerging from a review of the literature, of divergence between dose-response curves for effects on activity and attention. We predict that the dose that optimizes performance on ratings of hyperactivity-impulsivity will be lower than that which optimizes performance on ratings of attention. We will similarly examine whether differences in dose-response curves for specific functions extend to differences between subtypes in optimal dose. The final aim of the current study is to compare the IN and CB subtypes with respect to selected measures of neurocognitive function on placebo and in response to drug treatment. We predict that the IN subtype will perform more poorly on measures of spatial orienting and stimulus encoding, whereas the CB subtype will show greater deficits on measures of cognitive inhibitory control, and that both types of cognitive deficit will respond to drug treatment.